Individuals at risk of malnutrition or who are unable to obtain sufficient nutrients by enteral means must be fed intravenously. The use of total parenteral nutrition (TPN)--the administration of nutrients via a peripheral or central vein--has grown rapidly over the past several years. Unfortunately, infection is a potential major complication of TPN. This is of particular concern with malnourished an debilitated patients with compromised immune systems.
Microbiologic contamination of TPN mixtures may occur during preparation of the mixture, during administration, or via manipulation of the catheter. Accordingly, a total nutrient admixture (TNA) which contains all daily nutritional requirements in a single container is highly desirable because of the reduced likelihood of contamination due to the reduced number of manipulations of the intravenous delivery system. Reduced work loads of health care personnel are also a positive result of the use of single container TNA systems vis-a-vis conventional TPN systems requiring multiple nutrient containers. Typically, a TNA admixture contains three primary components: lipids in the form of an emulsion, glucose, and amino acids. Other components may include electrolytes, trace elements, and vitamins. The lipid emulsion is typically stabilized by an emulsifying agent such as a phospholipid which the filtering medium should not absorb.
While TNA systems offer the benefits noted above, one potential drawback is that the TNA system provides a better growth media for potentially pathogenic microorganisms. For example, the growth of fungal organisms, such as Candida albicans, in parenteral nutrient formulations poses an infectious threat because they are able to thrive in a variety of nutrient systems. Further, while Candida albicans has been shown to proliferate in both conventional TPN formulations and TNA admixtures, in at least one study growth was found to be stimulated in TNA admixtures. Similarly, studies have shown that TNA systems support bacterial growth significantly better than conventional TPN solutions.
In addition to the problems noted above, the lipid emulsion component results in the TNA admixture being opaque, making proper inspection of the mixture impossible. This may lead to a variety of problems including undetected fat particles having a size ranging from a few to as large as about 20 micrometers in diameter, creating the danger of fat embolus.
While problems with TNA systems have been recognized for some time, the benefits of such systems have been found to outweigh the attendant difficulties and their use has grown at a rapid rate. At present, in the vicinity of 80% of all TPN deliveries in Western Europe are in the form of TNA. The use of TNA systems also continues to expand in both the United States and Japan. Accordingly, there is an ongoing and growing need for means to alleviate difficulties with the use of TNA systems.
Attempts to alleviate the problems associated with TNA systems have focused on the use of membrane filters with pore ratings of 1.2 micrometers. While such filters are presently being used, they suffer from limitations. Specifically, such filters have limited flow capacity such that they exhibit excessive pressure buildup and plugging with concomitant limited onstream filter life. Excessive pressure build up is a serious problem with parenteral nutrient systems since the liquid nutrient is typically administered using a pump designed only to operate at relatively low pressures, e.g., less than 25 psi, typically less than 15 psi, and, in many applications, at less than 10 psi. Because these pumps are not engineered to operate at higher pressures, the parenteral fluid administration system typically includes an occlusion alarm which shuts down the pump at a relatively low pressure. Accordingly, excessive pressure build up and plugging of a filter device is a potentially serious problem. Additionally, membrane filters with pore ratings of 1.2 micrometers provide only limited ability to remove fine particulate and microbiological contaminants.
There is, therefore, a need for a filter device having an enhanced capability for filtration of fine particulate matter and microorganisms and having the capability of removing significant amounts of bacteria, the capacity to remove pyrogenic matter, such as bacterial endotoxins, and which, in addition, has a relatively high volumetric capacity, typically up to 3 liters of TNA at a flow rate of up to about 300 milliliters per hour, coupled with low pressure drop and, thus, good onstream life. Ideally, such a device would also have a relatively small hold up volume of about 5 cubic centimeters or less.